primary & secondary prevention in the older ... - rcp london

Primary & Secondary Preventionin the older adult

What’s the evidence ?

Dr Terry QuinnChief Scientist Office/Stroke Association Senior Lecturer

Institute Cardiovascular & Medical Sciences

@DrTerryQuinn [email protected]

Conflict of interest / disclosures

Honoraria, travel, research support:

Bayer

Boehringer Eingleheim,

Bristol Myers Squibb Pfizer Alliance


I am co-ordinating editor of Cochrane Dementia



…………and partial to a meta-analysis




I began training in Clinical Pharmacology





…………prone to talking about clinical trials






I am a Geriatrician






I am a Geriatrician

…………..so, may say something pragmatic

Donald

73 this year

Retired from business but still active

Non-smoker, tee-total

Overweight, high LDL cholesterol

BP 148/82

Concerns over cognition but scored will on screening test

Current meds: Atorvastatin 80mg

Doc, should I take a blood pressure tablet and aspirin?

Primary & secondary prevention in older adults with:

• Statins

• Antihypertensives

• Anti-thrombotics

• Other agents

• Lifestyle management

What should the next older adult cardiovascular RCT look like ?

Adverse

event

risk

1

10

100

0 2 4 6 8 10 12 14 16 18 20

number of drugs taken

percen

t o

f p

ati

en

ts w

ith

AD

R

Adverse

event

risk

CV risk

Framingham (cardiac risk model)

Sex

Age

Cholesterol

HDL

Blood pressure

Diabetes

Smoking

GRACE (ACS risk model)

Age

Heart Rate

Systolic BP

Creatinine

CCF (Killip)

TIMI (ACS risk model)

Age

Risk factors

Aspirin

Angina

ECG change

Cardiac enzymes

ABCD2 (TIA risk model)

Age

Systolic BP

Clinical features

Duration

Diabetes Mellitus

CHADS2 (AF risk model)

CCF

Hypertension

Age

Diabetes Mellitus

Stroke

Adverse

event

risk

CV risk

Trial

evidence

Donald

73 this year




BP 148/82




PROSPER RCT

N=5804

Around 3.5 years F.U

P: Age 70-82 years

I: Pravastatin 40mg

C: Placebo

O: CV events

Shepherd J ,

Lancet 2002

Any CV event

cardiac event

stroke

PROSPER RCT

N=5804


P: Age 70-82 years

I: Pravastatin 40mg

C: Placebo

O: CV events

Shepherd J ,

Lancet 2002

Shepherd J ,

Lancet 2002

Adverse

event

risk

CV risk

1o or 2o

prevention

Trial participant • Robust

• Cognitively intact

• Single morbidity

• Healthy lifestyle

http://www.hospitalmanagement.net/contractors/monitoring/delmar/


Trial participant • Robust

• Cognitively intact

• Single morbidity

• Healthy lifestyle

My patients • Frail

• Cognitive decline

• Multi-morbidity

• ‘Typical’ Glasgow



Adverse

event

risk

CV risk

1o or 2o

prevention

Frailty

Morbidty

Donald

73 this year




BP 148/82




RR

130 mmHg BP

Blood pressure and all cause mortality

RR

? 160 mmHg BP

Blood pressure and all cause mortality

Yue-Bin,

BMJ 2018

N=4658

Mean age 92.1 years

Three year follow-up

Yue-Bin,

BMJ 2018

Ettehad,

Lancet 2015

Xie X,

Lancet 2015

Severe hypotension 5 RCTs 0.3% vs 0.1% RR 2.68 (1.21-5.89)

Xie X,

Lancet 2015

Xie X,

Lancet 2015

Xie X,

Lancet 2015

Is this old?

Xie X,

Lancet 2015

Is this old?

Need to have

4 years left

Musini VM,

CDSR 2009

SPRINT RCT

N=9361


P: Age 68 (SD 9.4)

I: sBP<120mmHG

C: sBP <140mmHg

O: CV events

Hypotension 158 (3.4%) 93 (2.0) 1.7 <0.001

Syncope 163 (3.5%) 113 (2.4) 1.44 0.003

AKI 204 (4.4%) 120 (2.6%) 1.71 <0.001

E’lite abnormality 177 (3.8%) 129 (2.8%) 1.38 0.006

Disability

Mortality

M.A.C.E

Hospital admission

Treatment burden

Care-home

Cognitive declineBP

Adverse

event

risk

CV risk

What are

you trying

to prevent

Donald

73 this year




BP 148/82




ASPREE RCT

N=19,114


P: Age >70 (median 74)

I: Aspirin 100mg

C: Placebo

O: CV events

Any death

HR 1.14

(1.01-1.29)

Major bleed

8.6 per 1000

versus

6.2 per 1000

HR 1.38

(1.18-1.62)

Adverse

event

risk

CV risk

Should we be

stopping not

starting

Donald

73 this year




BP 148/82


ECG – atrial fibrillation



Primary prevention of stroke in AF

0

1

2

3

4

5

6

7

8

9

AFASK BAATAF CAFA SPAF SPINAF

No.

of s

trok

es (%

)

warfarin

control

AFAS=AF Aspirin Study

BAATAF=Boston Area Anticoag. Trial

CAF=Canadian AF anticoagulation

SPAF=Stroke prevention AF

SPINAF=Stroke prevention non-rheumatic AF

Anticoagulation underused in elderly

50% of AF pts > 75 years

<20% of pts in AF studies > 75 years

Anticoagulation underused in elderly

50% of AF pts > 75 years

<20% of pts in AF studies > 75 years

BAFTA trial – pragmatic, primary care trial

N=973; pts >75

ASA 75mg v. warfarin (INR 2-3)

Mant J Lancet

2007 370:493-503

BAFTA trial

0

0.5

1

1.5

2

2.5

3

3.5

4

Major stroke

(ASA)

Major stroke

(warfarin)

Major bleed

(ASA)

Major bleed

(warfarin)

(%)

even

ts

*

NNT 50

Stroke HR 0.48 (0.28 – 0.80)

Bleed HR 0.96 (0.53 – 1.75)

Pts age > 75

years

Apixaban(ARISTOTLE)

Dabigatran (RE-LY)

Edoxaban(ENGAGE AF-

TIMI 48)

Rivaroxaban(ROCKET AF)

Patients aged

> 75 years

5678

(31%)

7258

(40%)

8474

(40%)

6229

(44%)

Stroke/SE 0.71

(0.53-0.95)

0.67

(0.49-0.90)

0.83

(0.67-1.04)

0.80

(0.63-1.02)

Major bleed 0.64

(0.52-0.79)

1.18

(0.98-1.42)

0.83

(0.70-0.99)

1.11

(0.92-1.34)

Intracranial

bleed

0.34

(0.20-0.57)

0.42

(0.25-0.70)

0.40

(0.26-0.62)

0.80

(0.50-1.28)

GI bleeding Data not

available

1.79

(1.35-2.37)

1.32

(1.10-1.72)

Data not

available

Bo M

Eur J Int Med 2017

Adverse

event

risk

CV risk

Which agent

offers the

most benefit

Donald

73 this year




BP 148/82


TSH 9 mU/L, normal T4 and T3



To determine if there are multimodal clinical benefits from

levothyroxine treatment in older people with SCH

health-related quality of life,

cardiovascular disease,

muscle function, cognition, BP, BMI, waist circumference

Levothyroxine vs placebo

HR 0.89 (95%CI:0.47-1.69) p=0.728

ThyPRO39

Handgrip strength

Digit-symbol substitution

Cardiovascular events

Total and CVS mortality

Blood pressure

Body Mass Index

Weight

Waist circumference

Barthel index

IADL

ThyPRO39

Handgrip strength

Digit-symbol substitution

Cardiovascular events

Total and CVS mortality

Blood pressure

Body Mass index

Weight

Waist circumference

Barthel index

IADL

X

X

X

X

X

X

X

X

X

X

X

Adverse

event

risk

CV risk

Sometimes

there IS

enough

evidence

Donald

73 this year




BP 148/82




INTERSTROKE

Lancet 2010

}Explains around 85% of all ischaemic stroke

http://images.google.co.uk/imgres?imgurl=http://food.oregonstate.edu/images/fat/lard1.jpg&imgrefurl=http://food.oregonstate.edu/l/lard.html&h=380&w=639&sz=119&hl=en&start=3&tbnid=zR_R7oYA4o57fM:&tbnh=81&tbnw=137&prev=/images?q=lard&gbv=2&svnum=10&hl=en


}Explains around 90% of all ischaemic stroke



Adverse

event

risk

CV risk

There is more

to life than

drugs

Donald

73 this year




BP 148/82




Adverse

event

risk

CV risk

RCT

Evidence

Aspirin

Statin

BP drugs

Patients

Intervention

Control

Outcomes

Patients – frail?

Intervention

Control

Outcomes

Patients

Intervention – start or stop?

Control

Outcomes

Patients

Intervention – start or stop?

Control

Outcomes – not just death & MI

ASPREE RCT

N=19,114



I: Aspirin 100mg

C: Placebo

O: CV events

ASPREE RCT

N=19,114



I: Aspirin 100mg

C: Placebo

O: CV events

Dementia

Disability

ASPREE RCT

N=19,114



I: Aspirin 100mg

C: Placebo

O: CV events

Burton J,

Drugs & Ageing 2018

SPRINT RCT

N=9361


P: Age 68 (SD 9.4)

I: sBP<120mmHG

C: sBP <140mmHg

O: CV events

Primary & secondary prevention in older adults with:

• Statins

• Antihypertensives

• Anti-thrombotics

• Other agents

• Lifestyle management

What should the next older adult cardiovascular RCT look like ?

primary & secondary prevention in the older ... - rcp london

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